This invention relates to a composition and method for the treatment of porous bone such as osteoporotic bone.
The expression “porous bone” is intended herein to identify a condition of porosity and/or decreased bone mineral density that distinguishes the morphology of bone exhibiting a pathological condition from healthy bone. A common type of porous bone pathology is osteoporosis.
Osteoporosis is a pathologic state or disease involving some symptom or risk due to quantitative bone reduction exceeding a certain degree. Major symptoms are spinal kyphosis, fractures of dorsolumbar bones, vertebral centra, femoral necks, lower ends of radius, ribs, upper end of humerus, and others. In normal bone tissue, bone breakdown occurs constantly, but there is good balance between formation and resorption; osteoblasts and osteoclasts play key roles in bone formation and bone resorption, respectively. Upon deterioration of this balance, bone resorption surpasses bone formation, resulting in quantitative bone reduction.
Osteoporosis results in bone fractures in about 50% of postmenopausal women and is a leading cause of disability in an aging population. The decrease in bone mineral density and changes in architecture that accompany postmenopausal osteoporosis predisposes elderly women to fractures, particularly of the vertebral bodies. It is not elderly persons alone who suffer from this painful condition. Other individuals, such as transplant recipients, suffer fractures as a result of chronic steroid use. Current therapies include an adequate calcium and vitamin D intake as well as specific treatment with compounds such as estrogens, calcitonin and the bisphosphonates. However, each of these treatments has either troubling side effects or limited efficacy. Women fear the small increase in potential risk of breast cancer due to estrogens despite the dramatic reduction in myocardial infarctions and reduction in bone resorption. Calcitonin has a limited effect and is a protein and therefore needs to be injected or inhaled which is inconvenient. The new bisphosphonates such as alendronate have had encouraging results with an increase in bone density and decrease in fractures, however, some upper gastrointestinal irritation has been reported (Abraham et al., 1999, Mod. Pathol. Dec. 12(12): 1152-1157). Current research for new compounds has concentrated on the systemic administration of bone anabolic compounds such as parathyroid hormone (PTH) or fragments of PTH or locally acting cytokines or bone growth factors such as bone morphogenic proteins. When these therapies are unable to prevent fractures of porous bone, the victims of such fractures suffer from persistent, often excruciating pain, which significantly impairs mobility and quality of life. External bracing, analgesics, and observation may be all that is necessary for pain control in some patients, but in others, a constant requirement for narcotics can be as life altering as the fracture itself.
Vertebroplasty has been described in the literature as a method of injecting materials into vertebral bodies via a pedicle approach. Patients with various problems including osteoporosis, tumor or trauma have deficiencies of the vertebral body leading to pain or other complications. By injecting polymethyl methacrylate (bone cement) into these areas interventional radiologists or other physicians are able to avoid further subsidence of the vertebrae and alleviate pain. This procedure can be done on an outpatient basis, but currently is reserved for patients with major problems.
Vertebroplasty using injected polymethyl methacrylate suffers from the inability of the implant site to respond well to repeated stresses. Polymethyl methacrylate is a “dead” implant material which becomes brittle when subjected to repeat stresses. Bone repaired with this technique is little more than a bony shell filled with a hardened polymer.
Other methods of vertebroplastyd include the injection of granular, resorbable materials. These methods rely upon osteoinduction to provide long term strength, a process that requires time and is also susceptible to any influences that led to the initial formation of porous bone. Any bone tissue formed through osteoinduction at the implant site may be subsequently subjected to the same influences that produced the porous bone site in the first place.
Therefore, there is a need for an implant composition that is able to support physiological loads at the time of implantation and remain where placed even after it is incorporated into new tissue at the implant site. Success of the implant requires the contiguous growth of tissue to create a solid mass. The implant will be load bearing even while it is undergoing incorporation into new bony/fibrous tissue at the implant site.
Fibrous tissue, consisting primarily of fibrin and collagen proteins has been observed to infiltrate and encapsulate materials implanted into a body. The fibrous tissue can form a network of tissues that are resilient to applied forces and able to sustain physiological loads. Such a tissue network, being primarily soft tissue and containing few bone cells, would not be susceptible to those factors which lead to an increase in bone porosity and/or decrease in bone mineral density. Therefore, the implant, when eventually incorporated into fibrous tissue, would be expected to provide long term relief from the above described difficulties associated with porous bone conditions. In some applications, e.g., tumor defects, it may be advantageous to promote new bone growth at the graft site. An implant in accordance with the invention would provide load-bearing capabilities at the graft site before and during the formation of new bony tissue at the implantation site.
A flowable, and thus injectable, load-bearing composition that remains at the repair site during and after the formation of tissue at the site would be desirable.